MC3R

melanocortin 3 receptor, the group of Melanocortin receptors

Basic information

Region (hg38): 20:56248732-56249815

Links

ENSG00000124089 ∙ NCBI:4159 ∙ OMIM:155540 ∙ HGNC:6931 ∙ Uniprot:P41968 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• body mass index quantitative trait locus 9 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Obesity, severe, susceptibility to, 9	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine	11889220; 18231126; 21047972

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MC3R gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MC3R gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	5	1	10
missense			27		2	29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	31	5	3

Variants in MC3R

This is a list of pathogenic ClinVar variants found in the MC3R region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-56248851-C-T		MC3R-related disorder	Uncertain significance (Mar 28, 2024)
20-56248855-G-A			Uncertain significance (Aug 19, 2023)
20-56248868-T-A		MC3R-related disorder	Uncertain significance (May 30, 2024)
20-56248869-C-G		MC3R-related disorder	Uncertain significance (Oct 18, 2023)
20-56248880-A-G		See cases	Uncertain significance (Aug 16, 2022)
20-56248885-G-A		MC3R-related disorder	Likely benign (Jul 11, 2023)
20-56248888-T-A		MC3R-related disorder	Likely benign (Dec 28, 2021)
20-56248893-G-A			Uncertain significance (Apr 06, 2024)
20-56248909-A-G		MC3R-related disorder	Likely benign (Sep 18, 2019)
20-56248915-T-C		MC3R-related disorder	Likely benign (Jun 13, 2024)
20-56248922-A-C		not specified	Uncertain significance (May 25, 2022)
20-56248927-C-A		MC3R-related disorder	Uncertain significance (Nov 10, 2023)
20-56248933-C-A			Uncertain significance (Jan 18, 2024)
20-56248937-A-T		MC3R-related disorder	Likely benign (Jul 14, 2023)
20-56248939-C-T		MC3R-related disorder	Likely benign (Sep 18, 2019)
20-56248953-A-G		MC3R-related disorder	Uncertain significance (Jan 04, 2024)
20-56248970-G-A		not specified	Uncertain significance (Jun 12, 2023)
20-56248973-G-A			Benign (Jan 31, 2024)
20-56248977-T-C		MC3R-related disorder • See cases	Uncertain significance (Dec 20, 2021)
20-56248980-T-C		MC3R-related disorder	Uncertain significance (Apr 28, 2022)
20-56248982-T-A		not specified	Uncertain significance (May 27, 2022)
20-56248992-T-C		MC3R-related disorder	Uncertain significance (Aug 06, 2024)
20-56248994-G-C		Obesity	Likely benign (May 28, 2022)
20-56248994-G-T			Uncertain significance (Aug 01, 2023)
20-56248995-T-C		MC3R-related disorder	Uncertain significance (Mar 05, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MC3R	protein_coding	protein_coding	ENST00000243911	1	1084

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.99e-8	0.0528	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.140	201	195	1.03	0.0000129	2152
Missense in Polyphen		86	92.534	0.92939		1079
Synonymous	-0.193	91	88.7	1.03	0.00000729	660
Loss of Function	-1.14	9	6.00	1.50	2.66e-7	66

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for MSH (alpha, beta and gamma) and ACTH. This receptor is mediated by G proteins which activate adenylate cyclase. Required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for the normal regulation of circadian clock activity in the brain. {ECO:0000250|UniProtKB:P33033}.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);Peptide GPCRs;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;Ghrelin;G alpha (s) signalling events;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;GPCR downstream signalling (Consensus)

Intolerance Scores

• loftool: 0.486
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.135
• hipred: N
• hipred_score: 0.400
• ghis: 0.431

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.807

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mc3r
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; limbs/digits/tail phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of heart rate;G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger;adenylate cyclase-activating G protein-coupled receptor signaling pathway;phospholipase C-activating G protein-coupled receptor signaling pathway;regulation of blood pressure;circadian regulation of gene expression;homoiothermy;locomotor rhythm;sodium ion homeostasis;regulation of feeding behavior
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: melanocortin receptor activity;melanocyte-stimulating hormone receptor activity;protein binding;peptide hormone binding;neuropeptide binding